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  1. Article ; Online: The diagnostic accuracy of photopic negative responses evoked by broadband and chromatic stimuli in a clinically heterogeneous population.

    Leo, Shaun M / Neveu, Magella M / Yu-Wai-Man, Patrick / Mahroo, Omar A / Robson, Anthony G

    Documenta ophthalmologica. Advances in ophthalmology

    2023  Volume 147, Issue 3, Page(s) 165–177

    Abstract: Purpose: To compare the diagnostic accuracy of the photopic negative response (PhNR) elicited by red-blue (RB) and white-white (WW) stimuli, for detection of retinal ganglion cell (RGC) dysfunction in a heterogeneous clinical cohort.: Methods: Adults ...

    Abstract Purpose: To compare the diagnostic accuracy of the photopic negative response (PhNR) elicited by red-blue (RB) and white-white (WW) stimuli, for detection of retinal ganglion cell (RGC) dysfunction in a heterogeneous clinical cohort.
    Methods: Adults referred for electrophysiological investigations were recruited consecutively for this single-centre, prospective, paired diagnostic accuracy study. PhNRs were recorded to red flashes (1.5 cd·s·m
    Results: Two hundred and forty-three participants were initially enrolled, with 200 (median age 54; range 18-95; female 65%) meeting inclusion criteria. Sensitivity was 53% (95% confidence intervals [CI] 39% to 68%) and 62% (95% CI 48% to 76%), for WW and RB PhNRs, respectively. Specificity was 80% (95% CI 74% to 86%) and 78% (95% CI 72% to 85%), respectively. There was a statistically significant difference between sensitivities (p = 0.046) but not specificities (p = 0.08) of the two methods. Receiver operator characteristic (ROC) area under the curve (AUC) values were 0.73 for WW and 0.74 for RB PhNRs.
    Conclusion: PhNRs to red flashes on a blue background may be more sensitive than white-on-white stimuli, but there is no significant difference between specificities. This study highlights the value and potential convenience of using white-on-white stimuli, already used widely for routine ERG assessment.
    MeSH term(s) Adult ; Humans ; Female ; Middle Aged ; Electroretinography/methods ; Prospective Studies ; Evoked Potentials, Visual ; Retina/physiology ; Retinal Ganglion Cells/physiology ; Photic Stimulation
    Language English
    Publishing date 2023-10-27
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 212594-8
    ISSN 1573-2622 ; 0012-4486
    ISSN (online) 1573-2622
    ISSN 0012-4486
    DOI 10.1007/s10633-023-09956-5
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  2. Article ; Online: Retinal GABAergic Alterations in Adults with Autism Spectrum Disorder.

    Huang, Qiyun / Ellis, Claire L / Leo, Shaun M / Velthuis, Hester / Pereira, Andreia C / Dimitrov, Mihail / Ponteduro, Francesca M / Wong, Nichol M L / Daly, Eileen / Murphy, Declan G M / Mahroo, Omar A / McAlonan, Gráinne M

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2024  Volume 44, Issue 14

    Abstract: Alterations in γ-aminobutyric acid (GABA) have been implicated in sensory differences in individuals with autism spectrum disorder (ASD). Visual signals are initially processed in the retina, and in this study, we explored the hypotheses that the GABA- ... ...

    Abstract Alterations in γ-aminobutyric acid (GABA) have been implicated in sensory differences in individuals with autism spectrum disorder (ASD). Visual signals are initially processed in the retina, and in this study, we explored the hypotheses that the GABA-dependent retinal response to light is altered in individuals with ASD. Light-adapted electroretinograms were recorded from 61 adults (38 males and 23 females;
    MeSH term(s) Male ; Adult ; Female ; Humans ; Autism Spectrum Disorder/drug therapy ; Retina ; Electroencephalography ; gamma-Aminobutyric Acid ; Electroretinography
    Chemical Substances gamma-Aminobutyric Acid (56-12-2)
    Language English
    Publishing date 2024-04-03
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.1218-23.2024
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  3. Article ; Online: Cone-driven strong flash electroretinograms in healthy adults: Prevalence of negative waveforms.

    Jiang, Xiaofan / Bhatti, Taha / Tariq, Ambreen / Leo, Shaun M / Aychoua, Nancy / Webster, Andrew R / Hysi, Pirro G / Hammond, Christopher J / Mahroo, Omar A

    Documenta ophthalmologica. Advances in ophthalmology

    2023  Volume 148, Issue 1, Page(s) 25–36

    Abstract: Purpose: Both rod and cone-driven signals contribute to the electroretinogram (ERG) elicited by a standard strong flash in the dark. Negative ERGs usually reflect inner retinal dysfunction. However, in diseases where rod photoreceptor function is ... ...

    Abstract Purpose: Both rod and cone-driven signals contribute to the electroretinogram (ERG) elicited by a standard strong flash in the dark. Negative ERGs usually reflect inner retinal dysfunction. However, in diseases where rod photoreceptor function is selectively lost, a negative waveform might represent the response of the dark-adapted cone system. To investigate the dark-adapted cone-driven waveform in healthy individuals, we delivered flashes on a dim blue background, designed to saturate the rods, but minimally adapt the cones.
    Methods: ERGs were recorded, using conductive fibre electrodes, in adults from the TwinsUK cohort. Responses to 13 cd m
    Results: Mean (SD) participant age was 62.5 (11.3) years (93% female). ERGs from 203 right and 204 left eyes were included, with mean (SD) b/a ratios of 1.22 (0.28) and 1.18 (0.28), respectively (medians, 1.19 and 1.17). Proportions with negative waveforms were 23 and 26%, respectively. Right and left eye b/a ratios were strongly correlated (correlation coefficient 0.74, p < 0.0001). We found no significant correlation of b/a ratio with age.
    Conclusions: Over 20% of eyes showed b/a ratios less than 1, consistent with the notion that dark-adapted cone-driven responses to standard bright flashes can have negative waveforms. The majority had ratios greater than 1. Thus, whilst selective loss of rod function can yield a negative waveform (with reduced a-wave) in some, our findings also suggest that loss of rod function can occur without necessarily yielding a negative ERG. One potential limitation is possible mild cone system adaptation by the background.
    MeSH term(s) Adult ; Humans ; Female ; Middle Aged ; Male ; Electroretinography ; Prevalence ; Dark Adaptation ; Photic Stimulation ; Retinal Cone Photoreceptor Cells/physiology
    Language English
    Publishing date 2023-11-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 212594-8
    ISSN 1573-2622 ; 0012-4486
    ISSN (online) 1573-2622
    ISSN 0012-4486
    DOI 10.1007/s10633-023-09957-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Exploratory Study of the Association between the Severity of Idiopathic Intracranial Hypertension and Electroretinogram Photopic Negative Response Amplitude Obtained Using a Handheld Device.

    Raharja, Antony / Leo, Shaun M / Chow, Isabelle / Indusegaran, Mathura / Hammond, Christopher J / Mahroo, Omar A / Wong, Sui H

    Life (Basel, Switzerland)

    2021  Volume 11, Issue 5

    Abstract: The photopic negative response (PhNR) is a negative component of the photopic flash electroretinogram that follows the b-wave and is thought to arise from the retinal ganglion cells. Reduction in its amplitude in idiopathic intracranial hypertension (IIH) ...

    Abstract The photopic negative response (PhNR) is a negative component of the photopic flash electroretinogram that follows the b-wave and is thought to arise from the retinal ganglion cells. Reduction in its amplitude in idiopathic intracranial hypertension (IIH) has been previously documented using formal electroretinography. This study explored the use of a handheld device (RETeval, LKC technologies, Gaithersburg, MD, USA) in 72 IIH patients of varying stages and severity (and seven controls) and investigated associations between PhNR parameters and disease severity. PhNR amplitudes at 72 ms (P
    Language English
    Publishing date 2021-05-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life11050437
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  5. Article ; Online: Electrical responses from human retinal cone pathways associate with a common genetic polymorphism implicated in myopia.

    Jiang, Xiaofan / Xu, Zihe / Soorma, Talha / Tariq, Ambreen / Bhatti, Taha / Baneke, Alexander J / Pontikos, Nikolas / Leo, Shaun M / Webster, Andrew R / Williams, Katie M / Hammond, Christopher J / Hysi, Pirro G / Mahroo, Omar A

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 21, Page(s) e2119675119

    Abstract: Myopia is the commonest visual impairment. Several genetic loci confer risk, but mechanisms by which they do this are unknown. Retinal signals drive eye growth, and myopia usually results from an excessively long eye. The common variant most strongly ... ...

    Abstract Myopia is the commonest visual impairment. Several genetic loci confer risk, but mechanisms by which they do this are unknown. Retinal signals drive eye growth, and myopia usually results from an excessively long eye. The common variant most strongly associated with myopia is near the GJD2 gene, encoding connexin-36, which forms retinal gap junctions. Light-evoked responses of retinal neurons can be recorded noninvasively as the electroretinogram (ERG). We analyzed these responses from 186 adult twin volunteers who had been genotyped at this locus. Participants underwent detailed ERG recordings incorporating international standard stimuli as well as experimental protocols aiming to separate dark-adapted rod- and cone-driven responses. A mixed linear model was used to explore association between allelic dosage at the locus and international standard ERG parameters after adjustment for age, sex, and family structure. Significant associations were found for parameters of light-adapted, but not dark-adapted, responses. Further investigation of isolated rod- and cone-driven ERGs confirmed associations with cone-driven, but not rod-driven, a-wave amplitudes. Comparison with responses to similar experimental stimuli from a patient with a prior central retinal artery occlusion, and from two patients with selective loss of ON-bipolar cell signals, was consistent with the associated parameters being derived from signals from cone-driven OFF-bipolar cells. Analysis of single-cell transcriptome data revealed strongest GJD2 expression in cone photoreceptors; bipolar cell expression appeared strongest in OFF-bipolar cells and weakest in rod-driven ON-bipolar cells. Our findings support a potential role for altered signaling in cone-driven OFF pathways in myopia development.
    MeSH term(s) Electroretinography/methods ; Genome-Wide Association Study ; Humans ; Myopia/genetics ; Myopia/metabolism ; Polymorphism, Genetic ; Retinal Cone Photoreceptor Cells/metabolism ; Retinal Rod Photoreceptor Cells/metabolism
    Language English
    Publishing date 2022-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2119675119
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  6. Article ; Online: KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.

    Georgiou, Michalis / Robson, Anthony G / Fujinami, Kaoru / Leo, Shaun M / Vincent, Ajoy / Nasser, Fadi / Cabral De Guimarães, Thales Antônio / Khateb, Samer / Pontikos, Nikolas / Fujinami-Yokokawa, Yu / Liu, Xiao / Tsunoda, Kazushige / Hayashi, Takaaki / Vargas, Mauricio E / Thiadens, Alberta A H J / de Carvalho, Emanuel R / Nguyen, Xuan-Thanh-An / Arno, Gavin / Mahroo, Omar A /
    Martin-Merida, Maria Inmaculada / Jimenez-Rolando, Belen / Gordo, Gema / Carreño, Ester / Ayuso, Carmen / Sharon, Dror / Kohl, Susanne / Huckfeldt, Rachel M / Wissinger, Bernd / Boon, Camiel J F / Banin, Eyal / Pennesi, Mark E / Khan, Arif O / Webster, Andrew R / Zrenner, Eberhart / Héon, Elise / Michaelides, Michel

    American journal of ophthalmology

    2020  Volume 225, Page(s) 95–107

    Abstract: Purpose: To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults.: Study design: This was a multicenter international clinical cohort study.: Methods: Review of clinical ... ...

    Abstract Purpose: To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults.
    Study design: This was a multicenter international clinical cohort study.
    Methods: Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects.
    Results: In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades.
    Conclusion: In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics.
    MeSH term(s) Adolescent ; Adult ; Aged ; Alleles ; Child ; Child, Preschool ; Dark Adaptation/physiology ; Electroretinography ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Molecular Biology ; Phenotype ; Potassium Channels, Voltage-Gated/genetics ; Refraction, Ocular/physiology ; Retina/physiopathology ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/physiopathology ; Retrospective Studies ; Tomography, Optical Coherence ; Vision Disorders/diagnosis ; Vision Disorders/genetics ; Vision Disorders/physiopathology ; Visual Acuity/physiology ; Whole Exome Sequencing ; Whole Genome Sequencing
    Chemical Substances KCNV2 protein, human ; Potassium Channels, Voltage-Gated
    Language English
    Publishing date 2020-12-11
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80030-2
    ISSN 1879-1891 ; 0002-9394
    ISSN (online) 1879-1891
    ISSN 0002-9394
    DOI 10.1016/j.ajo.2020.11.022
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